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Research & Scholarship

Current Research and Scholarly Interests

My goal is to extend the benefits of organ transplant to greater numbers of patients while maintaining Stanford's excellent outcomes. We have set up a protocol to treat morbidly obese patients, who normally would not qualify for kidney transplant, with bariatric surgery prior to kidney transplantation. We are also developing the "paired-organ exchange" program at Stanford to increase the chances that patients with willing but incompatible living donors can still receive a living donor kidney.

Clinical Trials

Comparative Renal Function of Young (18-45 Years) and Ageing (55 Years and Above) Kidney DonorsRecruiting

It is our purpose in this study to compare the kidney structure and function of older
patients to that of young patients before and after removal of a single kidney for transplant
donation and to examine the remaining kidney's ability to adapt and maintain function over
time. More specifically, we aim to examine the effect of uninephrectomy on adaptive
hyperfiltration in the remaining kidney. A secondary aim is to investigate whether subjects
in the aging population undergo compensation to the same extent as younger subjects. We will
also examine the compensatory rise in GFR (glomerular filtration rate) that follows
uninephrectomy in both groups, and, again, compare the results in the aged versus young
subjects. This will help in delineating the extent to which the aging population can be a
potential source of living kidney donors for kidney transplantation.
It is also our purpose with this study to refine the tests to be used in the donor evaluation
process so as to accurately identify ideal candidates for safe kidney donation.

This research study is to determine if donor blood stem cells given after living, related,
HLA antigen (Ag) haplotype match or living, unrelated, 3 HLA antigen matched (HLA-A, -B, and
-DR) donor kidney transplantation will change the immune system such that immunosuppressive
drugs can be completely withdrawn or reduced to minimal dose without kidney rejection.

The Stanford Medical Center Program in Multi-Organ Transplantation and the Division of Bone
marrow Transplantation are enrolling patients into a research study to determine if donor
stem cells given after a living related one Haplotype match kidney transplantation will
change the immune system such that immunosuppressive drugs can be completely withdrawn.

The investigators hypothesize that the absorption of topically applied EFA-containing
emollient (SSO) into the skin and thence into the bloodstream in children with SAM will
improve skin barrier function and accelerate weight gain and clinical rehabilitation beyond
that possible through normal standard-of-care

Publications

All Publications

Abstract

Kidney paired donation strategies have facilitated compatible living-donor kidney transplants for end stage renal disease patients with willing but incompatible living donors. Success has inspired further innovations that expand opportunities for kidney-paired donation. Two such innovations are the advanced donation strategy in which a donor provides a kidney before their recipient is matched, or even in need of, a kidney transplant, and deceased donor initiated chains in which chains are started with deceased donors rather than altruistic living donors. While these innovations may expand kidney paired donation, they raise several ethical issues. Specific concerns raised by advanced donation include the management of uncertainty, the extent of donor and recipient consent, the scope of the obligation that the organization has to the kidney exchange paired recipient, the naming of alternative recipients, and the potential to unfairly advantage the recipient. Use of deceased donors for chain initiating kidneys raises ethical issues concerning the consent process for each involved party, the prioritization of deceased donor kidneys, the allocation of chain ending kidneys, and the value of a living donor kidney versus a deceased donor kidney. We outline each ethical issue and discuss how it can be conceptualized and managed so that these kidney paired donation innovations programs are ultimately successful.

Abstract

The process of taking a research project from conception to publication is one way to encourage surgeons to communicate hypothesis, critically assess literature and data, and defend research conclusions to a broad audience. The goal of this study was to define surgery resident publishing epidemiology and identify characteristics of residents and residency programs that might predict increased publication productivity.A survey was administered to eight general surgery residency programs to collect residency and resident variables from 1993-2013. The primary endpoint was the number of first-author publications produced per resident. Secondary endpoints included clinical setting at which the former resident was practicing, fellowship pursued, and manuscript quality.Between 1993 and 2013, 676 residents graduated, median age was 33 years (range: 29-43 years) and 182 (27%) were female. Three hundred and sixty-six (54%) residents produced 1229 first-author publications. Of these, 112 (31%) residents produced one manuscript, 125 (34%) produced two-three manuscripts, 107 (29%) produced four-nine manuscripts, and 22 (6%) produced 10 or more manuscripts. Publishing ?1 manuscript in residency was associated with a 1.5 (P = 0.01) increased odds of having attended a top-tier research institution for medical school and a 2.3 (P

Abstract

Incompatible living donor kidney transplant (ILDKT) has been established as an effective option for end stage renal disease (ESRD) patients with willing but HLA incompatible live donors, reducing mortality and improving quality of life. Depending upon antibody titer, ILDKT can require highly resource intensive procedure including intravenous immunoglobulin, plasma exchange and/or cell depleting antibody treatment as well as protocol biopsies and DSA testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT recipients (N=926) with varying antibody titers to matched compatible transplants (N=2762) performed between 2002-2011. Data were assembled from a national cohort study of ILDKT and a unique dataset linking hospital cost accounting data, and Medicare claims. Overall, ILDKT transplants were 41% more expensive than their compatible counterparts ($151,024 vs. $106,636, p

Abstract

Previous studies of resident attrition have variably included preliminary residents and likely overestimated categorical resident attrition. Whether program director attitudes affect attrition has been unclear.To determine whether program director attitudes are associated with resident attrition and to measure the categorical resident attrition rate.This multicenter study surveyed 21 US program directors in general surgery about their opinions regarding resident education and attrition. Data on total resident complement, demographic information, and annual attrition were collected from the program directors for the study period of July 1, 2010, to June 30, 2015. The general surgery programs were chosen on the basis of their geographic location, previous collaboration with some coauthors, prior work in surgical education and research, or a program director willing to participate. Only categorical surgical residents were included in the study; thus, program directors were specifically instructed to exclude any preliminary residents in their responses.Five-year attrition rates (2010-2011 to 2014-2015 academic years) as well as first-time pass rates on the General Surgery Qualifying Examination and General Surgery Certifying Examination of the American Board of Surgery (ABS) were collected. High- and low-attrition programs were compared.The 21 programs represented different geographic locations and 12 university-based, 3 university-affiliated, and 6 independent program types. Programs had a median (interquartile range [IQR]) number of 30 (20-48) categorical residents, and few of those residents were women (median [IQR], 12 [5-17]). Overall, 85 of 966 residents (8.8%) left training during the study period: 15 (17.6%) left after postgraduate year 1, 34 (40.0%) after postgraduate year 2, and 36 (42.4%) after postgraduate year 3 or later. Forty-four residents (51.8%) left general surgery for another surgical discipline, 21 (24.7%) transferred to a different surgery program, and 18 (21.2%) exited graduate medical education altogether. Each program had an annual attrition rate ranging from 0.73% to 6.0% (median [IQR], 2.5% [1.5%-3.4%]). Low-attrition programs were more likely than high-attrition programs to use resident remediation (21.0% vs 6.8%; P?.001). Median (IQR) Qualifying Examination pass rates (93% [90%-98%] vs 92% [86%-100%]; P?=?.92) and Certifying Examination pass rates (83% [68%-84%] vs 81% [71%-86%]; P?=?.47) were similar. Program directors at high-attrition programs were more likely than their counterparts at low-attrition programs to agree with this statement: "I feel that it is my responsibility as a program director to redirect residents who should not be surgeons."The overall 5-year attrition rate of 8.8% was significantly lower than previously reported. Program directors at low-attrition programs were more likely to use resident remediation. Variations in attrition may be explained by program director attitudes, although larger studies are needed to further define program factors affecting attrition.

Effect of match-run frequencies on the number of transplants and waiting times in kidney exchange.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant SurgeonsAshlagi, I., Bingaman, A., Burq, M., Manshadi, V., Gamarnik, D., Murphey, C., Roth, A. E., Melcher, M. L., Rees, M. A.2017

Abstract

Numerous kidney exchange (kidney paired donation [KPD]) registries in the United States have gradually shifted to high-frequency match-runs, raising the question of whether this harms the number of transplants. We conducted simulations using clinical data from 2 KPD registries-the Alliance for Paired Donation, which runs multihospital exchanges, and Methodist San Antonio, which runs single-center exchanges-to study how the frequency of match-runs impacts the number of transplants and the average waiting times. We simulate the options facing each of the 2 registries by repeated resampling from their historical pools of patient-donor pairs and nondirected donors, with arrival and departure rates corresponding to the historical data. We find that longer intervals between match-runs do not increase the total number of transplants, and that prioritizing highly sensitized patients is more effective than waiting longer between match-runs for transplanting highly sensitized patients. While we do not find that frequent match-runs result in fewer transplanted pairs, we do find that increasing arrival rates of new pairs improves both the fraction of transplanted pairs and waiting times.

Abstract

Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1,267 shipped and 205 non-shipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008-2015, compared to 4,800 unrelated, non-shipped, non-KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25 to 23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non-KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% CI: 1.02-1.09, p<0.01). However, there was not a significant association between CIT and all-cause graft failure (aHR: 1.01, 95% CI: 0.98-1.04, p=0.4), death-censored graft failure (aHR: 1.02, 95% CI: 0.98-1.06, p=0.4), or mortality (aHR 1.00, 95% CI: 0.96-1.04, p>0.9). This study of KPD-facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow-up are needed to refine our understanding of the safety of shipping donor kidneys through KPD. This article is protected by copyright. All rights reserved.

Abstract

With organs in short supply, only a limited number of kidney transplants can be performed a year. Live donor donation accounts for 1/3rd of all kidney transplants performed in the United States. Unfortunately, not every donor recipient pair is feasible because of Human leukocyte antigen (HLA) sensitization and ABO incompatibility. To overcome these barriers to transplant, strategies such as kidney paired donation (KPD) and desensitization have been developed. KPD is the exchange of donors between at least two incompatible donor-recipient pairs such that they are now compatible. Desensitization is the removal of circulating donor specific antibodies to prevent graft rejection. Regardless of the treatment strategy, highly sensitized patients whose calculated panel reactive antibody (cPRA) is ?95% remain difficult to transplant with match rates as low as 15% in KPD pools. Desensitization has proved to be difficult in those with high antibody titers. A novel approach is the combination of both KPD and desensitization to facilitate compatible and successful transplantation. A highly sensitized patient can be paired with a better immunological match in the KPD pool and subsequently desensitized to a lesser degree. This article reviews the current progress in KPD and desensitization and their use as a combined therapy.

Abstract

We sought to identify donor characteristics influencing long-term graft survival, expressed by a novel measure, kidney life years (KLYs), in living donor kidney transplantation (LDKT).Cox and multiple regression analyses were applied to data from the Scientific Registry for Transplant Research from 1987 to 2015. Dependent variable was KLYs.Living donor kidney transplantation (129 273) were performed from 1987 to 2013 in the United States. To allow sufficient time to assess long-term results, outcomes of LDKTs between 1987 and 2001 were analyzed. After excluding cases where a patient died with a functioning graft (8301) or those missing HLA data (9), 40 371 cases were analyzed. Of 18 independent variables, the focus became the 4 variables that were the most statistically and clinically significant in that they are potentially modifiable in donor selection (P <0.0001; ie, HLA match points, donor sex, donor biological sibling and donor age). HLA match points had the strongest relationship with KLYs, was associated with the greatest tendency toward graft longevity on Cox regression, and had the largest increase in KLYs (2.0 year increase per 50 antigen Match Points) based on multiple regression.In cases when a patient has multiple potential donors, such as through paired exchange, graft life might be extended when a donor with favorable matching characteristics is selected.

Abstract

We propose that some deceased donor (DD) kidneys be allocated to initiate nonsimultaneous extended altruistic donor chains of living donor (LD) kidney transplants to address, in part, the huge disparity between patients on the DD kidney waitlist and available donors. The use of DD kidneys for this purpose would benefit waitlisted candidates in that most patients enrolled in kidney paired donation (KPD) systems are also waitlisted for a DD kidney transplant, and receiving a kidney through the mechanism of KPD will decrease pressure on the DD pool. In addition, a LD kidney usually provides survival potential equal or superior to that of DD kidneys. If KPD chains that are initiated by a DD can end in a donation of an LD kidney to a candidate on the DD waitlist, the quality of the kidney allocated to a waitlisted patient is likely to be improved. We hypothesize that a pilot program would show a positive impact on patients of all ethnicities and blood types.

Abstract

Frailty is the concept of accumulating physiologic declines that make people less able to deal with stressors, including surgery. Prehabilitation is intervention to enhance functional capacity before surgery. Frailty and prehabilitation among transplant populations and the role of wearable fitness tracking devices (WFTs) in delivering fitness-based interventions will be discussed.Frailty is associated with increased complications, longer length of hospital stay and increased mortality after surgery. Frail kidney transplant patients have increased delayed graft function, mortality and early hospital readmission. Frail lung or liver transplant patients are more likely to delist or die on the waitlist. Prehabilitation can mitigate frailty and has resulted in decreased length of hospital stay and fewer postsurgical complications among a variety of surgical populations. Increasingly, WFTs are used to monitor patient activity and improve patient health. Interventions using WFTs have resulted in improved activity, weight loss and blood pressure.Frailty is a measurable parameter that identifies patients at risk for worse health outcomes and can be mitigated through intervention. Prehabilitation to reduce frailty has been shown to improve postsurgical outcomes in a variety of populations. WFTs are being integrated in healthcare delivery for monitoring and changing health behavior with promising results.

Abstract

A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or not a kidney from a deceased donor was received. The generalizability of that finding is unclear.In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group). We analyzed the data with and without patients from the highest-volume center in the study.Recipients of kidney transplants from incompatible live donors had a higher survival rate than either control group at 1 year (95.0%, vs. 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%) (P<0.001 for all comparisons with the two control groups). The survival benefit was significant at 8 years across all levels of donor-specific antibody: 89.2% for recipients of kidney transplants from incompatible live donors who had a positive Luminex assay for anti-HLA antibody but a negative flow-cytometric cross-match versus 65.0% for the waiting-list-or-transplant control group and 47.1% for the waiting-list-only control group; 76.3% for recipients with a positive flow-cytometric cross-match but a negative cytotoxic cross-match versus 63.3% and 43.0% in the two control groups, respectively; and 71.0% for recipients with a positive cytotoxic cross-match versus 61.5% and 43.7%, respectively. The findings did not change when patients from the highest-volume center were excluded.This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

We Need to Take the Next Step.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant SurgeonsMelcher, M. L., Roberts, J. P., Leichtman, A. B., Roth, A. E., Rees, M. A.2016

Abstract

To determine the influence of program strategies, such as program directors' (PD) attitudes about the American Board of Surgery In-Training Examination (ABSITE) and approach to ABSITE preparation, on residents' ABSITE performance.A 17-item questionnaire was sent to PDs at surgical residency programs. The questions were designed to elicit information regarding the educational curriculum, remediation protocols, and opinions relating to the ABSITE. Main outcome measure was categorical resident ABSITE percentile scores from the January 2014 examination. Statistical analysis was performed using the Student t-test, analysis of variance, and linear regression as appropriate.The study was carried out at general surgery residency programs across the country.In total, 15 general surgery residency PDs participated in the study.The PD response rate was 100%. All 460 resident ABSITE scores from the 15 programs were obtained. In total, 10 programs (67%) identified as university affiliated, 4 programs (27%) as independent academic, and 1 program (7%) as hybrid. The mean number of residents per program was 30.7 (range: 15-57). In total, 14 PDs (93%) indicated that an ABSITE review curriculum was in place and 13 PDs (87%) indicated they had a remediation protocol for residents with low ABSITE scores (with differing thresholds of <30th, <35th, and <40th percentile). The median overall ABSITE score for all residents was 61st percentile (interquartile range = 39.5). The mean ABSITE score for each program ranged from 39th to 75th percentile. Program factors associated with higher ABSITE scores included tracking resident reading throughout the year (median 63rd percentile with tracking vs 59th percentile without, p = 0.040) and the type of remediation (by PD: 77th percentile, by PD and faculty: 57th percentile, faculty only: 64th percentile, with Surgical Education and Self-Assessment Program (SESAP): 63rd percentile, outside review course: 43rd percentile; p < 0.001). Programs with a remediation protocol trended toward higher ABSITE scores compared with programs without remediation protocols (median 61st percentile vs 53rd percentile, p = 0.098). Factors not significantly associated with ABSITE performance included number of structured educational hours per week and frequency of ABSITE review sessions.Program factors appear to significantly influence ABSITE performance. Programs where the PD was actively involved in remediation mentorship and the tracking of resident reading achieved higher ABSITE percentile scores on the January 2014 examination. Counterintuitively, residents from programs with a lower ABSITE threshold for remediation performed better on the examination.

Abstract

Although kidney paired donation (KPD) has led to thousands of transplants, the 2012 KPD Consensus Conference concluded that more could be done. Perceptions are that a large number of match offers never resulted in transplantations, and unfruitful matches have both financial and emotional costs.To describe, quantify, and analyze the unrealized match offers, we studied the matching process from registration to transplantation in the National Kidney Registry, a large KPD registry, over a 25-month period.Of the 3,180 match offers, 454 were turned down. The most common reasons were the donor was not acceptable (50%) and their recipient had unacceptably high donor-specific antibodies (28%). Of the 2,228 accepted offers, 1,335 advanced to the cell-based cross-match stage because 893 of these were part of chains that fell through. Fifty-five of 887 recorded cell-based cross-matches were positive, 20 donors were unacceptable, and 22 recipients had unacceptably high donor-specific antibodies. Six hundred ninety transplantations were performed.Despite the success of KPD, by analyzing the matching process, we identify several strategies to increase the number of KPD transplantations, including recruiting more participants, processing the match offers more quickly at the transplant center level, enhancing the donor preselection tools, improving communication between centers and the registries, and combining desensitization with KPD.

Abstract

We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy.Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed.This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC.The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection.HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.

Is Informed Consent Enough?American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2015

Abstract

As illustrated by Flechner et al (1), patients with renal failure continue to benefit from rapid innovations within multiple Kidney Paired Donation (KPD) registries. The development of the Advanced Donation Program (ADP) facilitates transplants by enabling the donors to donate even when their intended recipients (IR) are not matched yet. However, as with any innovation, ADP introduces new challenges including risks to the IRs and registries, vagueness in the definition of priority granted to the IR, and concerns about fairness to the donor should the IR become untransplantable. This article is protected by copyright. All rights reserved.

Abstract

The 80-hour work-week limit for all residents was instituted in 2003 and studies looking at its effect have been mixed. Since the advent of the 16-hour mandate for postgraduate year 1 residents in July 2011, no data have been published regarding the effect of this additional work-hour restriction.To determine whether the 16-hour intern work limit, implemented in July 2011, has adversely affected operative experience.A retrospective review of categorical postgraduate year 1 Accreditation Council for Graduate Medical Education case logs from the intern class (N?=?52) (with 16-hour work limit) compared with the 4 preceding years (2007-2010; N?=?197) (without 16-hour work limit). A total of 249 categorical general surgery interns from 10 general surgery residency programs in the western United States were included.Total, major, first-assistant, and defined-category case totals.As compared with the preceding 4 years, the 2011-2012 interns recorded a 25.8% decrease in total operative cases (65.9 vs 88.8, P?=?.005), a 31.8% decrease in major cases (54.9 vs 80.5, P?.001), and a 46.3% decrease in first-assistant cases (11.1 vs 20.7, P?=?.008). There were statistically significant decreases in cases within the defined categories of abdomen, endocrine, head and neck, basic laparoscopy, complex laparoscopy, pediatrics, thoracic, and soft tissue/breast surgery in the 16-hour shift intern era, whereas there was no decrease in trauma, vascular, alimentary, endoscopy, liver, and pancreas cases.The 16-hour work limit for interns, implemented in July 2011, is associated with a significant decrease in categorical intern operative experience. If the 16-hour shift were to be extended to all postgraduate year levels, one can anticipate that additional years of training will be needed to maintain the same operative volume.

Abstract

While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 29-30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.

Abstract

HYPOTHESIS In July 2011, surgical interns were prohibited from being on call from home by the new residency review committee guidelines on work hours. In support of the new Accreditation Council for Graduate Medical Education work-hour restrictions, we expected that a period of intern home call would correlate with increased rates of postoperative morbidity and mortality. DESIGN Prospective cohort. SETTING University-affiliated tertiary Veterans Affairs Medical Center. PATIENTS All patients identified in the Veterans Affairs National Surgical Quality Improvement Program database who underwent an operation performed by general, vascular, urologic, or cardiac surgery services between fiscal years (FYs) 1999 and 2010 were included. MAIN OUTCOME MEASURES During FYs 1999-2003, the first call for all patients went to an in-hospital intern. In the subsequent period (FYs 2004-2010), the first call went to an intern on home call. Thirty-day unadjusted morbidity and mortality rates and risk-adjusted observed to expected ratios were analyzed by univariate analysis and joinpoint regression, respectively. RESULTS Unadjusted overall morbidity rates decreased between 1999-2003 and 2004-2010 (12.14% to 10.19%, P = .003). The risk-adjusted morbidity observed to expected ratios decreased at a uniform annual percentage change of -6.03% (P < .001). Unadjusted overall mortality rates also decreased between the 2 periods (1.76% to 1.26%; P = .05). There was no significant change in the risk-adjusted mortality observed to expected ratios during the study. CONCLUSIONS The institution of an intern home call schedule was not associated with increased rates of postoperative morbidity or mortality.

Abstract

The objectives of this study were to evaluate and compare the performance of the deceased donor registries of the 50 states and the District of Columbia and to identify possible predictive factors of donor designation. Data were collected retrospectively by Donate Life America using a questionnaire sent to Donor Designation Collaborative state teams between 2007 and 2010. By the end of 2010, there were 94,669,081 designated donors nationwide. This accounted for 39.8 per cent of the U.S. population aged 18 years and over. The number of designated organ donors and registry-authorized recovered donors increased each year; however, the total number of recovered donors in 2010 was the lowest since 2004. Donor designation rate was significantly higher when license applicants were verbally questioned at the Department of Motor Vehicles (DMV) regarding their willingness to register as a donor and when DMV applicants were not given an option on DMV application forms to contribute money to support organ donation, compared with not being questioned verbally, and being offered an option to contribute money. State registries continue to increase the total number of designated organ donors; however, the current availability of organs remains insufficient to meet the demand. These data suggest that DMV applicants who are approached verbally regarding their willingness to register as a donor and not given an option on DMV application forms to contribute money to support organ donation might be more likely to designate themselves to be a donor.

Abstract

Despite the potential for altruistic nondirected donors (NDDs) to trigger multiple transplants through nonsimultaneous transplant chains, concerns exist that these chains siphon NDDs from the deceased donor wait list and that donors within chains might not donate after their partner receives a transplant.To determine the number of transplantations NDDs trigger through chains.Retrospective review of large, multicenter living donor-recipient database.Fifty-seven US transplant centers contributing donor-recipient pairs to the database.The NDDs initiating chain transplantation.Number of transplants per NDD.Seventy-seven NDDs enabled 373 transplantations during 46 months starting February 2008. Mean chain length initiated by NDDs was 4.8 transplants (median, 3; range, 1-30). The 40 blood type O NDDs triggered a mean chain length of 6.0 (median, 4; range, 2-30). During the interval, 66 of 77 chains were closed to the wait list, 4 of 77 were ongoing, and 7 of 77 were broken because bridge donors became unavailable. No chains were broken in the last 15 months, and every recipient whose incompatible donor donated received a kidney. One hundred thirty-three blood type O recipients were transplanted. CONCLUSION AND RELEVANCE: This large series demonstrates that NDDs trigger almost 5 transplants on average, more if the NDD is blood type O. There were more blood type O recipients than blood type O NDDs participating. The benefits of transplanting 373 patients and enabling others without living donors to advance outweigh the risk of broken chains that is decreasing with experience. Even 66 patients on the wait list without living donors underwent transplantation with living-donor grafts at the end of these chains.

Abstract

Sensitization remains a major barrier to kidney transplantation. Sensitized patients comprise 30% of the kidney transplant waiting list but fewer than 15% of highly sensitized patients are transplanted each year. Options for highly sensitized patients with an immunologically incompatible living donor include desensitization or kidney paired donation (KPD). However, these options when used alone may still not be sufficient to allow a compatible transplant for recipients who are broadly sensitized with cumulative calculated panel-reactive antibody (cPRA) > 95%. We describe in this report the combined use of both desensitization and KPD to maximize the likelihood of finding a compatible match with a more immunologically favorable donor through a kidney exchange program. This combined approach was used in five very highly sensitized patients, all with cPRA 100%, who ultimately received compatible living and deceased donor kidney transplants. We conclude that early enrollment in paired kidney donor exchange and tailored desensitization protocols are key strategies to improve care and rates of kidney transplantation in highly sensitized patients.

Abstract

We conducted a systematic review of published literature to gain a better understanding of the impact of advanced fellowships on surgical resident training and education.As fellowship opportunities rise, resident training may be adversely impacted.PubMed, MEDLINE, Scopus, BIOSIS, Web of Science, and a manual search of article bibliographies. Of the 139 citations identified through the initial electronic search and screened for possible inclusion, 23 articles were retained and accepted for this review. Data were extracted regarding surgical specialty, methodology, sample population, outcomes measured, and results.Eight studies retrospectively compared the eras before and after the introduction of a fellowship or trended data over time. Approximately half used data from a single institution, whereas the other half used some form of national data or survey. Only 3 studies used national case data. Fourteen studies looked at general surgery, 6 at obstetrics-gynecology, 2 at urology, and 1 at otolaryngology. Only one study concluded that fellowships have a generally positive impact on resident education, whereas 9 others found a negative impact. The remaining 13 studies found mixed results (n = 6) or minimal to no impact (n = 7).The overall impact of advanced surgical fellowships on surgical resident education and training remains unclear, as most studies rely on limited data of questionable generalizability. A careful study of the national database of surgery resident case logs is essential to better understand how early surgical specialization and fellowships will impact the future of general surgery education.

Abstract

We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross-matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O-patients receiving a transplant (n = 90) was greater than the number of blood type O-non-directed donors (n = 32) initiating chains. We have 1-year follow up on the first 100 transplants. The mean 1-year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.

Abstract

To determine the rates and predictors of remediation and attrition among general surgery residents.Eleven-year retrospective analysis of 348 categorical general surgery residents at 6 West Coast programs.Rates and predictors of remediation and attrition.Three hundred forty-eight categorical general surgery residents were included. One hundred seven residents (31%) required remediation, of which 27 were remediated more than once. Fifty-five residents (15.8%) left their programs, although only 2 were owing to failed remediation. Remediation was not a predictor of attrition (20% attrition for those remediated vs 15% who were not [P = .40]). Remediation was most frequently initiated owing to a deficiency in medical knowledge (74%). Remediation consisted of monthly meetings with faculty (79%), reading assignments (72%), required conferences (27%), therapy (12%), and repeating a clinical year (6.5%). On univariate analysis, predictors of remediation included receiving honors in the third-year surgery clerkship, United States Medical Licensing Examination (USMLE) step 1 and/or step 2, and American Board of Surgery In-Training Examination scores at postgraduate years 1 through 4. On multivariable regression analysis, remediation was associated with receiving honors in surgery (odds ratio, 1.9; P = .01) and USMLE step 1 score (odds ratio, 0.9; P = .02). On univariate analysis, the only predictor of attrition was the American Board of Surgery In-Training Examination score at the postgraduate year 3 level (P = .04).Almost one third of categorical general surgery residents required remediation during residency, which was most often owing to medical knowledge deficits. Lower USMLE step 1 scores were predictors of the need for remediation. Most remediated residents successfully completed the program. Given the high rates of remediation and the increased educational burden on clinical faculty, medical schools need to focus on better preparing students to enter surgical residency.

Abstract

The presence of kidney stones has been a relative contraindication for living donation. With the widespread use of more sensitive imaging techniques as part of the routine living donor workup, kidney stones are more frequently detected, and their clinical significance in this setting is largely unknown. Records from 325 potential kidney donors who underwent MRA or CT-angiography were reviewed; 294 proceeded to donation. The prevalence of kidney stones found incidentally during donor evaluation was 7.4% (24 of 325). Sixteen donors with stones proceeded with kidney donation. All incidental calculi were nonobstructing and small (median 2 mm; range 1-9 mm). Eleven recipients were transplanted with allografts containing stones. One recipient developed symptomatic nephrolithasis after transplantation. This recipient was found to have newly formed stones secondary to hyperoxaluria, suggesting a recipient-driven propensity for stone formation. The remaining ten recipients have stable graft function, postoperative ultrasound negative for nephrolithiasis, and no sequelae from stones. No donor developed symptomatic nephrolithiasis following donation. Judicious use of allografts with small stones in donors with normal metabolic studies may be acceptable, and careful follow-up in recipients of such allografts is warranted.

Abstract

An increasing number of morbidly obese patients with end stage renal disease (ESRD) are sequentially undergoing bariatric surgery followed by renal transplantation. Discrepancies between the nutritional recommendations for obesity and chronic kidney disease (CKD) are often confusing for the obese patient in renal failure. However, when recommendations are structured according to stage and treatment of disease, a consistent plan can be clearly communicated to the patient. Therefore, to optimize patient and graft outcomes we present nutritional recommendations tailored to three patient populations: obese patients with ESRD, patients post Roux-en-Y gastric bypass (RYGBP) with ESRD, and patients post RYGBP and post renal transplantation.

Abstract

Kidney donor exchanges enable recipients with immunologically incompatible donors to receive compatible living donor grafts; however, the financial management of these exchanges, especially when an organ is shipped, is complex and thus has the potential to impede the broader implementation of donor exchange programs. Representatives from transplant centers that utilize the National Kidney Registry database to facilitate donor exchange transplants developed a financial model applicable to paired donor exchanges and donor chain transplants. The first tenet of the model is to eliminate financial liability to the donor. Thereafter, it accounts for the donor evaluation, donor nephrectomy hospital costs, donor nephrectomy physician fees, organ transport, donor complications and recipient inpatient services. Billing between hospitals is based on Medicare cost report defined costs rather than charges. We believe that this model complies with current federal regulations and effectively captures costs of the donor and recipient services. It could be considered as a financial paradigm for the United Network for Organ Sharing managed donor exchange program.

Abstract

Optimizing the possibilities for kidney-paired donation (KPD) requires the participation of donor-recipient pairs from wide geographic regions. Initially it was envisaged that donors would travel to the recipient center; however, to minimize barriers to participation and simplify logistics, recent trends have involved transporting the kidneys rather than the donors. The goal of this study was to review outcomes of this practice. KPD programs throughout the United States were directly queried about all transplants involving live donor kidney transport. Early graft function was assessed by urine output in the first 8 h, postoperative serum creatinine trend, and incidence of delayed graft function. Between April 27, 2007 and April 29, 2010, 56 live donor kidneys were transported among 30 transplant centers. Median CIT was 7.2 h (IQR 5.5-9.7, range 2.5-14.5). Early urine output was robust (>100 cc/h) in all but four patients. Creatinine nadir was <2.0 mg/dL in all (including the four with lower urine output) but one patient, occurring at a median of 3 days (IQR 2-5, range 1-49). No patients experienced delayed graft function as defined by the need for dialysis in the first week. Current evidence suggests that live donor kidney transport is safe and feasible.

Abstract

Tasocitinib (CP-690,550) is an orally active Janus kinase inhibitor that is in development for prophylaxis of acute rejection after kidney transplantation and for the treatment of select autoimmune diseases. The current study was conducted to evaluate the systemic exposure of mycophenolic acid (MPA) in de novo kidney transplant patients when coadministered with tasocitinib compared with exposure in patients receiving tacrolimus, which has no effect on MPA pharmacokinetics. Plasma MPA concentrations were obtained from 17 adult patients who received either 15 mg or 30 mg tasocitinib twice daily (eight patients) or tacrolimus (nine patients) after kidney transplantation. All patients also received concomitant mycophenolate mofetil, prednisone, and basiliximab induction. The median mycophenolate mofetil dose was 1000 mg twice daily. A two-compartment population pharmacokinetic model estimating oral clearance, between-patient variability in oral clearance, central volume of distribution, and residual variability in combination with historical estimates of first-order absorption rate constant, intercompartmental clearance, and peripheral volume of distribution adequately described the sparse MPA data. Based on individual estimates oral clearance from the population pharmacokinetic model, mean steady-state area under the concentration-time curve values for a mycophenolate mofetil dose of 1000 mg twice daily were 63 mg·hr/L (22%) and 59 mg·hr/L (36%) for the tasocitinib and tacrolimus groups, respectively. These results indicate that tasocitinib does not influence systemic MPA exposure.

Abstract

We sought to determine factors that predict the successful surgical repair of biliary complications after adult living donor liver transplantation (ALDLT).Records of 82 consecutive ALDLT right lobe recipients were reviewed. Operations were performed on 19 recipients for biliary complications. Post-operative biliary complications were analyzed. Fisher's exact test was used to identify variables that correlated with successful surgical repair.A total of 29 recipients had biliary complications, of which 19 had a surgical repair. The five recipients, operated on for a stricture without history of leaks, did not develop further complications. However, nine of 14 with a history of a leak developed further complications after surgical repair (p-value = 0.044). All five who presented with a biliary complication more than 100 d after transplant had successful surgical repair; however, nine out of 13 who presented within 57 d had additional complications after repair.Operations for strictures after ALDLT are more successful than operations for leaks. Recipients with isolated biliary strictures after ALDLT can be managed surgically; however, recipients with history of a leak often require additional interventions after surgical repair.

Abstract

Adult living-donor liver transplantation (ALDLT) has a high rate of biliary complications. We identified risk factors that correlate with biliary leaks and strictures by combining data from two centers. Records of ALDLT right lobe recipients (n = 156) at two centers between December 1998 and February 2005 were reviewed. Leak rate was analyzed in 144 recipients after we excluded those with hepatic artery thrombosis or death within 30 d of transplant. Stricture rate was also analyzed in 132 recipients after we excluded those with graft survival or follow-up <180 d. Biliary reconstructions were performed using either duct-to-duct (DD) or Roux-en-Y hepaticojejunostomy and were subclassified by anatomic type, number of anastomoses performed, and stent use. Prevalence of a leak and/or a stricture was 39%; 11% of recipients developed both. Single DD anastomoses between the graft right hepatic duct to the recipient common duct had significantly lower incidence of leaks compared to all other anastomotic types. Early leak was predictive of late stricture development (p = 0.006), but recipient demographics, diagnosis, warm ischemia time, anastomosis type, duct number, year of transplant, stent use, and transplant center were not. The results suggest donors with a single right hepatic duct reconstructed to the recipient common bile duct are the most likely to avoid biliary problems after ALDLT.

Abstract

We sought to determine whether US Medical Licensing Examination (USMLE) Step 1 score, American Board of Surgery (ABS) In-Training Examination (ABSITE) score, and other variables are associated with failing the ABS qualifying and certifying examinations. Identifying such factors may assist in the early implementation of an academic intervention for at-risk residents.Retrospective review.Seventeen general surgery training programs in the western United States.Six hundred seven residents who graduated in 2000-2007.First-time pass rates on the qualifying and certifying examinations, US vs non-US medical school graduation, USMLE Steps 1 and 2 scores, ABSITE scores, operative case volume, fellowship training, residency program type, and mandatory research.The first-time qualifying and certifying examination pass rates for the 607 graduating residents were 78% and 74%, respectively. On multivariable analysis, scoring below the 35th percentile on the ABSITE at any time during residency was associated with an increased risk of failing both examinations (odds ratio, 0.23 [95% confidence interval, 0.08-0.68] for the qualifying examination and 0.35 [0.20-0.61] for the certifying examination), as was scoring less than 200 on the USMLE Step 1 (0.36 [0.21-0.62] for the qualifying examination and 0.62 [0.42-0.93] for the certifying examination). A mandatory research year was associated with an increased likelihood of passing the certifying examination (odds ratio, 3.3 [95% confidence interval, 1.6-6.8]).Residents who are more likely to fail the ABS qualifying and certifying examinations can be identified by a low USMLE Step 1 score and by poor performance on the ABSITE at any time during residency. These findings support the use of the USMLE Step 1 score in the surgical residency selection process and a formal academic intervention for residents who perform poorly on the ABSITE.

Abstract

The organ donor shortage has been the most important hindrance in getting listed patients transplanted. Living kidney donors who are incompatible with their intended recipients are an untapped resource for expanding the donor pool through participation in transplant exchanges. Chain transplantation takes this concept further, with the potential to benefit even more recipients. We describe the first asynchronous, out of sequence transplant chain that was initiated by transcontinental shipment of an altruistic donor kidney 1 week after that recipient's incompatible donor had already donated his kidney to the next recipient in the chain. The altruistic donor kidney was transported from New York to Los Angeles and functioned immediately after transplantation. Our modified-sequence asynchronous transplant chain (MATCH) enabled eight recipients, at four different institutions, to benefit from the generosity of one altruistic donor and warrants further exploration as a promising step toward addressing the organ donor shortage.

Abstract

There is increasing evidence that obesity, independently from other comorbidities such as diabetes and hypertension, can cause renal dysfunction. While this indolent dysfunction may be asymptomatic, it can render patients more susceptible to renal insufficiency when the kidneys are further injured by other pathological processes. Here, we present a morbidly obese patient whose type-A aortic dissection was complicated by acute renal failure that subsequently progressed into end-stage renal disease. However, his renal function improved dramatically following substantial weight reduction after gastric bypass surgery obviating the need for dialysis and transplantation. The potential mechanisms by which a patient's obesity may lead to renal dysfunction are discussed. This case and other similar reports suggest that obese patients with renal failure can safely undergo bariatric surgery and that bariatric surgery may have a role in treating chronic kidney disease in select morbidly obese patients.

Abstract

There is a rapidly growing population of immunocompromised organ transplant recipients. These patients are at risk of a large variety of infections that have significant consequences on mortality, graft dysfunction, and graft loss. The diagnosis and treatment of these infections are facilitated by an understanding of the preoperative, perioperative, and postoperative risk factors; the typical pathogens; and their characteristic time of presentation. On the basis of these factors, we put forth an algorithm for diagnosing and treating suspected infections in solid organ transplant recipients.

Abstract

HIV-infected patients are increasingly referred for kidney transplantation, and may be at an increased risk for rejection. Treatment for rejection frequently includes thymoglobulin. We studied thymoglobulin's effect on CD4+ T-cell count, risk of infection and rejection reversal in 20 consecutive HIV-infected kidney recipients. All patients used antiretroviral therapy and opportunistic infection prophylaxis. Maintenance immunosuppression consisted of prednisone, mycophenolate mofetil and cyclosporine. Eleven patients received thymoglobulin (7 for rejection and 4 for delayed/slow graft function) while 9 did not. These two groups were similar in age, gender, race, donor characteristics and immunosuppression. Mean CD4+ T-cell counts remained stable in patients who did not receive thymoglobulin, but became profoundly suppressed in those who did, decreasing from 475 +/- 192 to 9 +/- 10 cells/microL (p < 0.001). Recovery time ranged from 3 weeks to 2 years despite effective HIV suppression. Although opportunistic infections were successfully suppressed, low CD4+ T-cell count was associated with increased risk of serious infections requiring hospitalization. Rejection reversed in 6 of 7 patients receiving thymoglobulin. We conclude that thymoglobulin reverses acute rejection in HIV-infected kidney recipients, but produces profound and long-lasting suppression of the CD4+ T-cell count associated with increased risk of infections requiring hospitalization.

Abstract

The role of antibody-mediated rejection (AMR) in pancreas transplantation is poorly understood. Here, we report on a patient who developed AMR of his pancreas allograft after receiving a simultaneous pancreas-kidney transplant. Pre-operative enhanced cytotoxicity and flow cytometry T-cell crossmatches were negative; B-cell crossmatches were not performed as per institutional protocol. The patient's post-operative course was significant for elevated serum amylase levels and development of hyperglycemia approximately 1 month after transplantation. A pancreatic biopsy at this time showed no cellular infiltrate but strong immunofluorescent staining for C4d in the interacinar capillaries. Analysis of the patient's serum identified donor-specific HLA-DR alloantibodies. He received intravenous immunoglobulin (IVIg), rituximab and plasmapheresis, and his pancreatic function normalized. We conclude that clinically significant AMR can develop in a pancreas allograft and recommend that pancreatic biopsies be assessed for C4d deposition if the patient has risk factors for AMR and/or the pathologic evidence for cell-mediated rejection is underwhelming.

Abstract

Concern exists as to the safety of laparoscopic donor nephrectomy (LDN) compared with open donor nephrectomy. Reported complications of LDN include emergent conversion to an open procedure, repeated surgery for postoperative bleeding, and even death. We hypothesize that LDNs can be performed safely, with a complication rate comparable with that of open donor nephrectomies.Case series and review of the literature.Tertiary care university hospital.Five hundred thirty kidney donors.An LDN performed without hand assistance, with the kidney extracted through a low transverse incision.Mean operative time, requirement for transfusion, intraoperative complications, and postoperative complications.This series includes 84 right-sided donor nephrectomies, 86 donors with a body mass index greater than 30 (calculated as weight in kilograms divided by the square of height in meters), and 91 donors with complex vascular anatomy. Mean donor age was 40 years (range, 18-73 years), and mean +/- SD operative time was 196 +/- 43 minutes. The only conversion occurred early in the series, and there have been 525 subsequent cases without the need for conversion or repeated surgery. There were no donor deaths. Five donors (0.9%) required perioperative blood transfusions. Overall complication rate was 6.4%, including 14 minor wound infections, 2 bowel injuries, 1 case of prolonged ileus, 3 splenic injuries, 2 bladder infections, 1 bladder injury, 1 case of rhabdomyolysis, 1 case of pneumonia, and 2 thromboembolic events.This series demonstrates that LDN can be performed at least as safely as open donor nephrectomy, with minimal bleeding and few postoperative complications.

Abstract

Gastric carcinoid tumors occur in 15% to 50% of patients with multiple endocrine neoplasia-1/Zollinger-Ellison syndrome (MEN-1/ZES) but are thought to be benign. We report 5 patients with MEN-1/ZES with symptomatic, aggressive gastric carcinoid tumors that required surgical procedures.This was a retrospective chart review.Each patient had MEN-1/ZES. Each patient had innumerable gastric carcinoid tumors with symptoms. The fasting gastrin level was 47,000 pg/mL (normal, <200 pg/mL); the basal acid output was 79 mEq/hr (n = 3), and the age at surgical exploration was 47 +/- 6 years, with a duration of MEN-1 of 21 +/- 3 years and of ZES of 15 +/- 2 years. All patients had elevated 5-HIAA or serotonin levels. Somatostatin receptor scintigraphy showed increased stomach uptake in 4 patients (80%). Four patients had a total gastrectomy; 4 patients had lymph node metastases removed, and 3 patients had liver metastases resected. One patient who did not have a total gastrectomy had liver carcinoid metastases.These results demonstrate that gastric carcinoid tumors in patients with longstanding MEN-1/ZES may be symptomatic, aggressive, and metastasize to the liver. With increased long-term medical treatment and life expectancy, these tumors will become an important determinant of survival.

Abstract

The full-thickness skin erosion (rupture) of an umbilical hernia in a patient with end-stage liver disease can lead to significant morbidity and mortality. Here, we present a case report of the use of a novel technique to treat a patient with this condition. The use of a fibrin-based tissue adhesive provides a means of managing such patients medically.

Abstract

The CLK1 gene of Saccharomyces cerevisiae encodes a 610-residue protein kinase that resembles known type II Ca2+/calmodulin-dependent protein kinases (CaM kinases), including the CMK1 and CMK2 gene products from the same yeast. The Clk1 kinase domain is preceded by a 162-residue N-terminal extension, followed by a 132-residue C-terminal extension (which contains a basic segment resembling known calmodulin-binding sites) and is as similar to mammalian CaM kinase (38% identity to rat CaM kinase alpha) as it is to yeast CaM kinase (37% identity to Cmk2). However, Clk1 shares 52% identity with Rck1, another putative protein kinase encoded in the S. cerevisiae genome. Clk1 tagged with a c-myc epitope (expressed in yeast) and a GST-Clk1 fusion (expressed in bacteria) underwent autophosphorylation and phosphorylated an exogenous substrate (yeast protein synthesis elongation factor 2), primarily on Ser. Neither Clk1 activity was stimulated by purified yeast calmodulin (CMD1 gene product), with or without Ca2+; no association of Clk1 with Cmd1 was detectable by other methods. C-terminally truncated Clk1(Delta487-610) was growth-inhibitory when overexpressed, whereas catalytically inactive Clk1(K201R Delta487-610) was not, suggesting that the C terminus is a negative regulatory domain. Using immunofluorescence, Clk1 was localized to the cytosol and excluded from the nucleus. A clk1Delta mutant, a clk1Delta rck1Delta double mutant, a clk1Delta cmk1Delta cmk2Delta triple mutant, and a clk1Delta rck1Delta cmk1Delta cmk2Delta quadruple mutant were all viable and manifested no other overt growth phenotype.